Objectives: The overall objective of the proposed CDA-2, ?Understanding and targeting stress reactivity in women Veterans with alcohol misuse?, is for the candidate to receive mentored training on, and to develop skills for, conducting research among women Veterans. Women are expected to comprise 35% of the U.S. Veteran population by 2035, making them the fastest growing segment of VHA users. Within this growing population, understanding their particular clinical needs will become increasingly important. Alcohol misuse is one clinical issue salient for women Veterans. Recent estimates of lifetime alcohol use disorder among women Veterans are up to 27%, equaling those of their male counterparts and exceeding those of civilian women, and women with alcohol misuse have high rates of co-occurring posttraumatic stress disorder (PTSD). Training goals of the CDA-2 grant include learning novel research methods, neurobiological markers of stress and addiction, advanced statistics, and professional development, all within the context of improving care for women Veterans. Aims for the study proposed in this CDA-2 project are two-fold: 1. conduct a randomized trial testing the effects of an emotion regulation skill (cognitive reappraisal) on stress-induced drinking among women with alcohol misuse and varying levels of co-occurring PTSD; 2. examine whether progesterone levels and/or severity of co-occurring PTSD ? factors which impact women?s stress reactivity and emotion regulation ? moderate the effectiveness of the cognitive reappraisal in reducing stress-induced drinking. Research has shown that serum levels of progesterone and its metabolites are associated with less stress reactivity, less alcohol craving and use, and better ability to regulate emotion. Women with PTSD, however, exhibit a deficit in progesterone metabolism, and women?s alcohol use and craving has been shown to fluctuate across the menstrual cycle. This research suggests that women with low progesterone levels, within the context of menstrual cycle phase or co-occurring PTSD, may be particularly prone to stress-induced drinking and may benefit from learning and using effective emotion regulation skills. Methods: The proposed study will use innovative methodology, combining experimental sessions in a randomized trial with daily longitudinal data collection. Each woman Veteran (n=60) will be randomized to one of two conditions: a control condition (n=30) or a condition in which participants learn to use cognitive reappraisal to regulate stress and negative emotion (n=30). Women in the cognitive reappraisal condition will be asked to practice and use this skill over a 35-day period (to encompass an entire menstrual cycle), and will complete daily logs of alcohol use and stress. Each participant will come in for two experimental sessions, scheduled at the time of her peak and lowest progesterone levels, during which participants in the cognitive reappraisal condition will use that skill in response to a personalized stress induction. Throughout these sessions, the effect of cognitive reappraisal on the following variables (after the stress induction) will be assessed: (1) alcohol craving, (2) inhibitory (cognitive) control, and (3) physiological arousal (heart rate variability). These three variables, and (4) stress-induced drinking during the 35-day period, will be the main study outcome variables. Results/Implications: Results from this study will enhance knowledge of at-risk groups of Veterans (women Veterans with mental health conditions) with Veteran-salient illnesses (PTSD and alcohol misuse) and advance the field of personalized medicine to improve the effectiveness of treatment. The study uses a novel approach (?microintervention? design) which isolates therapeutic strategies typically taught in larger therapeutic protocols, to understand their effects. The training and experiences included in this CDA-2 will provide the candidate with skills and knowledge in studying stress, substance use, and cognitive control among women Veterans. The line of research and training will facilitate the candidate?s career development, accelerating her progression in becoming a women?s health researcher in the VA.